Ion Entry/Exit Device

ABSTRACT

A method of introducing and ejecting ions from an ion entry/exit device ( 4 ) is disclosed. The ion entry/exit device ( 4 ) has at least two arrays of electrodes ( 20,22 ). The device is operated in a first mode wherein DC potentials are successively applied to successive electrodes of at least one of the electrode arrays (( 20,22 ) in a first direction such that a potential barrier moves along the at least one array in the first direction and drives ions into and/or out of the device in the first direction. The device is also operated in a second mode, wherein DC potentials are successively applied to successive electrodes of at least one of the electrode arrays ( 20,22 ) in a second, different direction such that a potential barrier moves along the array in the second direction and drives ions into and/or out of the device in the second direction. The device provides a single, relatively simple device for manipulating ions in multiple directions. For example, the device may be used to load ions into or eject ions from an ion mobility separator in a first direction, and may then be used to cause ions to move through the ion mobility separator in the second direction so as to cause the ions to separate.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority from and the benefit of United Kingdompatent application No. 1406575.9 filed on 11 Apr. 2014 and Europeanpatent application No. 14164500.2 filed on 11 Apr. 2014. The entirecontents of these applications are incorporated herein by reference.

BACKGROUND TO THE PRESENT INVENTION

Existing ion mobility separators generally operate in-line with the ionoptical path of a mass spectrometer and so have a direct impact on theoverall length of the instrument and also must be transited even if ionmobility separation is not required, potentially making timing betweenrapidly changing ion signals and subsequent analysers more problematic.This becomes more problematic as the length of ion mobility separator isincreased in order to increase the resolution of the device.

It is known to separate ions in closed-loop separators in order toovercome the problem of having to provide a relatively long device inorder to obtain the required resolution. However, it is desired toprovide an improved technique for introducing and extracting ions fromsuch a device and also for causing ions to begin to move around such adevice.

It is desired to provide an improved method of introducing and ejectingions from an ion mobility separation device, an improved ion entry/exitdevice, and an improved mass spectrometer or ion mobility spectrometer.

SUMMARY OF THE PRESENT INVENTION

From a first aspect, the present invention provides a method ofintroducing and ejecting ions from an ion mobility separation device,said method comprising:

providing an ion entry/exit device having at least two arrays ofelectrodes;

operating the device in a first mode, wherein DC potentials aresuccessively applied to successive electrodes of at least one of theelectrode arrays in a first direction such that a potential barriermoves along the at least one array in the first direction and drivesions into and/or out of the device in the first direction; and

operating the device in a second mode, wherein DC potentials aresuccessively applied to successive electrodes of at least one of theelectrode arrays in a second, different direction such that a potentialbarrier moves along the at least one array in the second direction anddrives ions into and/or out of the device in the second direction.

The present invention provides a single, relatively simple device formanipulating ions in multiple directions. For example, the device may beused to load ions into or eject ions from an ion mobility separator in afirst direction, and may then be used to cause ions to move through theion mobility separator in the second direction so as to cause the ionsto separate. The device may also be used to bypass the separator in thefirst direction. This removes the need for multiple regions tomanipulate ions.

The at least two arrays of electrodes may be arranged parallel to eachother.

Both of said arrays may be simultaneously operated in either said firstor second modes. Alternatively, only one of said arrays may be operatedin the first mode and only one other array may be operated in the secondmode.

Each array of electrodes may comprise a plurality of electrodes arrangedin rows and columns. Each row may comprise x electrodes, wherein x isselected from the group consistingof: >3; >4; >5; >6; >7; >8; >9; >10; >15; >20; >25; >30; >35; >40; >45;and >50. Additionally, or alternatively, each column may comprise yelectrodes, wherein y is selected from the group consistingof: >3; >4; >5; >6; >7; >8; >9; >10; >15; >20; >25; >30; >35; >40; >45;and >50. Any combination of number of electrodes per row and number ofelectrodes per column may be selected from the above lists.

Each array of electrodes may comprise a plurality of electrodes arrangedin rows and columns. In said first mode said DC potentials may beapplied to the electrodes in a first row and may then be successivelyapplied to different rows of electrodes such that said potential barriermoves along the array in the first direction. Alternatively, oradditionally, in said second mode said DC potentials may be applied tothe electrodes in a first column and may then be successively applied todifferent columns of electrodes such that said potential barrier movesalong the array in the second direction.

As described above, each array may have a plurality of electrodesarranged in each row and in each column. This arrangement isparticularly advantageous wherein each array operates in both the firstand second modes. Less preferably, one array operates in the first modeand another array operates in the second mode. In such an arrangement,one array may comprise only a column of electrodes arranged in the firstdirection for driving ions in the first direction in the first mode ofoperation, i.e. there is only one electrode in each row. Another arraymay comprise only a row of electrodes arranged in the second directionfor driving ions in the second direction in the second mode ofoperation, i.e. there is only one electrode in each column.

The method may further comprise supplying RF voltages to said arrays ofelectrodes so as to confine ions in the direction between the arrays.

The same phase RF potential may be applied to all of the electrodes inthe same column of electrodes, and adjacent columns of electrodes may bemaintained at different RF phases, such as opposite RF phases.Alternatively, the same phase RF potential may be applied to all of theelectrodes in the same row and adjacent rows of electrodes may bemaintained at different RF phases, such as opposite RF phases.

The first direction and second directions may be orthogonal to eachother. For example, the first and second directions may be aligned withthe directions of the columns and rows respectively.

The method may be operated in the first mode so as to load ions into thedevice in the first direction, and the method may then be operated insaid second mode so as to eject these ions from the device in the seconddirection.

The method may comprise temporally separating ions according to aphysicochemical property prior to their entry into the ion entry/exitdevice; then receiving the ions in the ion entry/exit device; operatingthe ion entry/exit device in the first mode so that the temporallyseparated ions are ejected from the device in the first direction; andtemporarily operating the ion entry/exit device in the second mode so asto selectively eject ions having a selected value, or range of values,of said physicochemical property from the device in the seconddirection. The physicochemical property may be mass to charge ratio orion mobility.

The method may further comprise ejecting said ions from the ionentry/exit device into a first ion guide, ion trap or ion processingdevice in said first mode and into a second ion guide in the secondmode.

The second ion guide may comprise electrodes and the method may compriseapplying DC voltages to the electrodes of the second ion guide so as todrive ions along the longitudinal axis of the second ion guide; andwherein either a static DC potential gradient is applied along the axiallength of the second ion guide so as to drive ions along saidlongitudinal axis; or wherein one or more DC potentials is applied tosuccessive electrodes along the axial length of the second ion guidesuch that a DC potential barrier travels along the length of the secondion guide and drives ions along the second ion guide.

The second ion guide may be a closed-loop ion guide that starts and endswith said ion entry/exit device such that in the second mode ions aredriven out of the ion entry/exit device through an exit aperture, passaround the closed-loop ion guide and are then reintroduced back into theion entry/exit device through an entrance aperture.

The second mode of operation may continue to operate such that thepotential barrier in the ion entry/exit region moves in the seconddirection and urges the reintroduced ions out of the ion entry/exitdevice in the second direction again so that the ions and pass aroundthe ion guiding region again.

The ions may be caused to pass around the ion guide and through the ionentry/exit region a plurality of times, and as many times as desired.For example, the ions may pass around the second ion guide and throughthe ion entry/exit region ≥x times, wherein x is 2, 3, 4, 5, 6, 7, 8, 9,10, 15 or 20.

A DC potential may be travelled around the second ion guide so as todrive ions from the exit aperture of the ion entry/exit device to theentrance aperture of the ion entry/exit device, and this travelling DCpotential may be synchronised with the travelling DC potential presentin the ion entry/exit device in the second mode of operation such that atravelling DC potential travels substantially continuously around thesecond ion guide and through the ion entry/exit device.

The travelling DC potential may travel substantially continuously aroundthe second ion guide and through the ion entry/exit device at a constantspeed.

The ion entry/exit device and/or second ion guide may form an ionmobility separator in which the ions separate along the longitudinalaxis according to their ion mobilities.

The ion entry/exit device may be operated in a mode so as to eject atleast some of the separated ions out of the device in the firstdirection and into said first ion guide, ion trap, or ion processingdevice. Alternatively, one or more additional ion entry/exit deviceshaving the construction described herein may be provided for ejecting atleast some of the separated ions out of the second ion guide and into afirst ion guide, ion trap, or ion processing device. Any one of theseion entry/exit devices may have the following features.

The ions may separate according to their ion mobilities as they passalong the second ion guide, and the ion entry/exit device may then beswitched to the first mode so as to eject at least some of the separatedions out of the device in the first direction and into said first ionguide, ion trap, or ion processing device.

The ion entry/exit device may be temporarily switched from the secondmode to the first mode such that only ions of a first ion mobility, orfirst range of ion mobilities, that have passed along the second ionguide are ejected out of the ion entry/exit device in the firstdirection, whilst other ions having a second ion mobility, or secondrange of ion mobilities, pass through the ion entry/exit device in thesecond direction such that they continue on to pass through the secondion guide again.

The selectively ejected ions may be stored, mass analysed, fragmented toform fragment ions, or reacted with ions or molecules to form productions within said first ion guide, ion trap, or ion processing device.

The method may comprise reintroducing the selectively ejected ions,fragment ions or product ions into the ion entry/exit device whilstoperating the device in the second mode such that the reintroduced ionspass into the second ion guide again.

The method may comprise operating the ion entry/exit device in the firstmode of operation such that ions are transmitted into, through and outof the ion entry/exit device in the first direction and into the firstion guide or ion trap, without being passed into said second ion guide.

During said first mode, the method may comprise maintaining thepotential of at least some of the electrodes in at least one of theelectrode arrays at a DC potential that is lower than the DC potentialof the electrodes in the adjacent portion(s) of the second ion guide,such that a DC potential barrier is provided between the ion entry/exitdevice and the second ion guide which prevents ions from exiting the ionentry/exit device and entering the second ion guide. Alternatively, oradditionally, during said second mode, the method may comprisemaintaining the potential of at least some of the electrodes in at leastone of the electrode arrays at a DC potential that is substantially thesame as the DC potential of the electrodes in the adjacent portion(s) ofthe second ion guide such that substantially no DC potential barrier isprovided between the ion entry/exit device and the second ion guide sothat ions can exit the ion entry/exit device and enter the second ionguide.

It is contemplated that the ion entry/exit device of the presentinvention may comprise only one array of electrodes.

Accordingly, from a second aspect the present invention provides amethod of introducing and ejecting ions from an ion entry/exit device,said method comprising:

providing an ion entry/exit device having at least one array ofelectrodes;

operating the device in a first mode, wherein DC potentials aresuccessively applied to successive electrodes of the electrode array ina first direction such that a potential barrier moves along the array inthe first direction and drives ions into and/or out of the device in thefirst direction; and

operating the device in a second mode, wherein DC potentials aresuccessively applied to successive electrodes of the electrode array ina second, different direction such that a potential barrier moves alongthe array in the second direction and drives ions into and/or out of thedevice in the second direction.

The method according to the second aspect may operate in any mannerdescribed herein in relation to the first aspect of the presentinvention, except wherein only a single array of electrodes may be used.

Ions may be held against the single array by applying a force to theions in a direction towards the array. This maintains the ions proximalto the array such that the potentials applied to the array are able tomove the ions. The force may be applied, for example, by a DC potential,an RF pseudo-potential or a gas flow.

The present invention also provides a method of mass spectrometry and/orion mobility spectrometry comprising a method as described herein. Themethod may further comprise detecting the ions, mass analysing the ionsor ion mobility analysing the ions.

The present invention also provides a method of mass spectrometry or ionmobility spectrometry comprising:

providing a closed loop ion guide having an ion entry/exit regionarranged therein, wherein the ion entry/exit region comprises at leasttwo arrays of electrodes;

operating the ion entry/exit region in a first mode, wherein DCpotentials are successively applied to successive electrodes of at leastone of the electrode arrays in a first direction such that a potentialbarrier moves along the at least one array in the first direction anddrives ions into and/or out of the closed loop ion guide in the firstdirection; and

operating the ion entry/exit region in a second mode, wherein DCpotentials are successively applied to successive electrodes of at leastone of the electrode arrays in a second, different direction such that apotential barrier moves along the at least one array in the seconddirection and drives ions around the longitudinal axis of the closedloop ion guide, and wherein the ions separate according to their ionmobilities as they pass around the closed loop ion guide.

This method may have any one or combination of the optional or preferredfeatures described herein in relation to the first aspect of the presentinvention.

The first aspect of the present invention also provides an ionentry/exit device for a mass spectrometer and/or ion mobilityspectrometer, said device comprising:

at least two arrays of electrodes;

at least one DC voltage supply; and

control means for varying the electrical potentials applied to theelectrodes of said at least two arrays with time;

wherein in a first mode of operation said control means successivelyapplies DC potentials to successive electrodes of at least one of theelectrode arrays in a first direction such that a potential barriermoves along the at least one array in the first direction for drivingions into and/or out of the device in the first direction; and

wherein in a second mode of operation said control means successivelyapplies DC potentials to successive electrodes of at least one of theelectrode arrays in a second, different direction such that a potentialbarrier moves along the at least one array in the second direction fordriving ions into and/or out of the device in the second direction.

The device may be arranged and configured to perform any of the methodsdescribed herein.

The second aspect the present invention also provides an ion entry/exitdevice for a mass spectrometer and/or ion mobility spectrometer, saiddevice comprising:

at least one array of electrodes;

at least one DC voltage supply; and

control means for varying the electrical potentials applied to theelectrodes of said at least one array with time;

wherein in a first mode of operation said control means successivelyapplies DC potentials to successive electrodes of the at least one arrayin a first direction such that a potential barrier moves along the atleast one array in the first direction for driving ions into and/or outof the device in the first direction; and

wherein in a second mode of operation said control means successivelyapplies DC potentials to successive electrodes of the at least one arrayin a second, different direction such that a potential barrier movesalong the at least one array in the second direction for driving ionsinto and/or out of the device in the second direction.

The present invention also provides a closed loop ion guide comprisingan ion entry/exit device, wherein said ion entry/exit device comprises:

at least two arrays of electrodes;

at least one DC voltage supply; and

control means for varying the electrical potentials applied to theelectrodes of said at least two arrays with time;

wherein in a first mode of operation said control means successivelyapplies DC potentials to successive electrodes of at least one of theelectrode arrays in a first direction such that a potential barriermoves along the at least one array in the first direction for drivingions into and/or out of the closed loop ion guide in the firstdirection; and

-   -   wherein in a second mode of operation said control means        successively applies DC potentials to successive electrodes of        at least one of the electrode arrays in a second, different        direction such that a potential barrier moves along the at least        one array in the second direction for driving ions around the        longitudinal axis of the closed loop ion guide such that the        ions separate according to their ion mobilities as they pass        around the closed loop ion guide.

The present invention also provides a mass spectrometer and/or ionmobility spectrometer comprising an ion entry/exit device or closed loopion guide as described herein.

The ion entry/exit device and/or closed loop ion guide and/orspectrometer may be configured so as to perform any one of the methodsdescribed herein.

The spectrometer may comprise:

(a) an ion source selected from the group consisting of: (i) anElectrospray ionisation (“ESI”) ion source; (ii) an Atmospheric PressurePhoto Ionisation (“APPI”) ion source; (iii) an Atmospheric PressureChemical Ionisation (“APCI”) ion source; (iv) a Matrix Assisted LaserDesorption Ionisation (“MALDI”) ion source; (v) a Laser DesorptionIonisation (“LDI”) ion source; (vi) an Atmospheric Pressure Ionisation(“API”) ion source; (vii) a Desorption Ionisation on Silicon (“DIOS”)ion source; (viii) an Electron Impact (“EI”) ion source; (ix) a ChemicalIonisation (“CI”) ion source; (x) a Field Ionisation (“FI”) ion source;(xi) a Field Desorption (“FD”) ion source; (xii) an Inductively CoupledPlasma (“ICP”) ion source; (xiii) a Fast Atom Bombardment (“FAB”) ionsource; (xiv) a Liquid Secondary Ion Mass Spectrometry (“LSIMS”) ionsource; (xv) a Desorption Electrospray Ionisation (“DESI”) ion source;(xvi) a Nickel-63 radioactive ion source; (xvii) an Atmospheric PressureMatrix Assisted Laser Desorption Ionisation ion source; (xviii) aThermospray ion source; (xix) an Atmospheric Sampling Glow DischargeIonisation (“ASGDI”) ion source; (xx) a Glow Discharge (“GD”) ionsource; (xxi) an Impactor ion source; (xxii) a Direct Analysis in RealTime (“DART”) ion source; (xxiii) a Laserspray Ionisation (“LSI”) ionsource; (xxiv) a Sonicspray Ionisation (“SSI”) ion source; (xxv) aMatrix Assisted Inlet Ionisation (“MAII”) ion source; (xxvi) a SolventAssisted Inlet Ionisation (“SAII”) ion source; (xxvii) a DesorptionElectrospray Ionisation (“DESI”) ion source; and (xxviii) a LaserAblation Electrospray Ionisation (“LAESI”) ion source; and/or

(b) one or more continuous or pulsed ion sources; and/or

(c) one or more ion guides; and/or

(d) one or more ion mobility separation devices and/or one or more FieldAsymmetric Ion Mobility Spectrometer devices; and/or

(e) one or more ion traps or one or more ion trapping regions; and/or

(f) one or more collision, fragmentation or reaction cells selected fromthe group consisting of: (i) a Collisional Induced Dissociation (“CID”)fragmentation device; (ii) a Surface Induced Dissociation (“SID”)fragmentation device; (iii) an Electron Transfer Dissociation (“ETD”)fragmentation device; (iv) an Electron Capture Dissociation (“ECD”)fragmentation device; (v) an Electron Collision or Impact Dissociationfragmentation device; (vi) a Photo Induced Dissociation (“PID”)fragmentation device; (vii) a Laser Induced Dissociation fragmentationdevice; (viii) an infrared radiation induced dissociation device; (ix)an ultraviolet radiation induced dissociation device; (x) anozzle-skimmer interface fragmentation device; (xi) an in-sourcefragmentation device; (xii) an in-source Collision Induced Dissociationfragmentation device; (xiii) a thermal or temperature sourcefragmentation device; (xiv) an electric field induced fragmentationdevice; (xv) a magnetic field induced fragmentation device; (xvi) anenzyme digestion or enzyme degradation fragmentation device; (xvii) anion-ion reaction fragmentation device; (xviii) an ion-molecule reactionfragmentation device; (xix) an ion-atom reaction fragmentation device;(xx) an ion-metastable ion reaction fragmentation device; (xxi) anion-metastable molecule reaction fragmentation device; (xxii) anion-metastable atom reaction fragmentation device; (xxiii) an ion-ionreaction device for reacting ions to form adduct or product ions; (xxiv)an ion-molecule reaction device for reacting ions to form adduct orproduct ions; (xxv) an ion-atom reaction device for reacting ions toform adduct or product ions; (xxvi) an ion-metastable ion reactiondevice for reacting ions to form adduct or product ions; (xxvii) anion-metastable molecule reaction device for reacting ions to form adductor product ions; (xxviii) an ion-metastable atom reaction device forreacting ions to form adduct or product ions; and (xxix) an ElectronIonisation Dissociation (“EID”) fragmentation device; and/or

(g) a mass analyser selected from the group consisting of: (i) aquadrupole mass analyser; (ii) a 2D or linear quadrupole mass analyser;(iii) a Paul or 3D quadrupole mass analyser; (iv) a Penning trap massanalyser; (v) an ion trap mass analyser; (vi) a magnetic sector massanalyser; (vii) Ion Cyclotron Resonance (“ICR”) mass analyser; (viii) aFourier Transform Ion Cyclotron Resonance (“FTICR”) mass analyser; (ix)an electrostatic mass analyser arranged to generate an electrostaticfield having a quadro-logarithmic potential distribution; (x) a FourierTransform electrostatic mass analyser; (xi) a Fourier Transform massanalyser; (xii) a Time of Flight mass analyser; (xiii) an orthogonalacceleration Time of Flight mass analyser; and (xiv) a linearacceleration Time of Flight mass analyser; and/or

(h) one or more energy analysers or electrostatic energy analysers;and/or

(i) one or more ion detectors; and/or

(j) one or more mass filters selected from the group consisting of: (i)a quadrupole mass filter; (ii) a 2D or linear quadrupole ion trap; (iii)a Paul or 3D quadrupole ion trap; (iv) a Penning ion trap; (v) an iontrap; (vi) a magnetic sector mass filter; (vii) a Time of Flight massfilter; and (viii) a Wien filter; and/or

(k) a device or ion gate for pulsing ions; and/or

(l) a device for converting a substantially continuous ion beam into apulsed ion beam.

The spectrometer may comprise either:

(i) a C-trap and a mass analyser comprising an outer barrel-likeelectrode and a coaxial inner spindle-like electrode that form anelectrostatic field with a quadro-logarithmic potential distribution,wherein in a first mode of operation ions are transmitted to the C-trapand are then injected into the mass analyser and wherein in a secondmode of operation ions are transmitted to the C-trap and then to acollision cell or Electron Transfer Dissociation device wherein at leastsome ions are fragmented into fragment ions, and wherein the fragmentions are then transmitted to the C-trap before being injected into themass analyser; and/or

(ii) a stacked ring ion guide comprising a plurality of electrodes eachhaving an aperture through which ions are transmitted in use and whereinthe spacing of the electrodes increases along the length of the ionpath, and wherein the apertures in the electrodes in an upstream sectionof the ion guide have a first diameter and wherein the apertures in theelectrodes in a downstream section of the ion guide have a seconddiameter which is smaller than the first diameter, and wherein oppositephases of an AC or RF voltage are applied, in use, to successiveelectrodes.

The spectrometer may comprise a device arranged and adapted to supply anAC or RF voltage to the electrodes. The AC or RF voltage preferably hasan amplitude selected from the group consisting of: (i) <50 V peak topeak; (ii) 50-100 V peak to peak; (iii) 100-150 V peak to peak; (iv)150-200 V peak to peak; (v) 200-250 V peak to peak; (vi) 250-300 V peakto peak; (vii) 300-350 V peak to peak; (viii) 350-400 V peak to peak;(ix) 400-450 V peak to peak; (x) 450-500 V peak to peak; and (xi) >500 Vpeak to peak.

The AC or RF voltage preferably has a frequency selected from the groupconsisting of: (i) <100 kHz; (ii) 100-200 kHz; (iii) 200-300 kHz; (iv)300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz; (vii) 1.0-1.5 MHz;(viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x) 2.5-3.0 MHz; (xi) 3.0-3.5 MHz;(xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz; (xiv) 4.5-5.0 MHz; (xv) 5.0-5.5MHz; (xvi) 5.5-6.0 MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0 MHz; (xix)7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii) 8.5-9.0 MHz;(xxiii) 9.0-9.5 MHz; (xxiv) 9.5-10.0 MHz; and (xxv) >10.0 MHz.

The spectrometer may comprise a chromatography or other separationdevice upstream of an ion source. According to an embodiment thechromatography separation device comprises a liquid chromatography orgas chromatography device. According to another embodiment theseparation device may comprise: (i) a Capillary Electrophoresis (“CE”)separation device; (ii) a Capillary Electrochromatography (“CEC”)separation device; (iii) a substantially rigid ceramic-based multilayermicrofluidic substrate (“ceramic tile”) separation device; or (iv) asupercritical fluid chromatography separation device.

The ion guide is preferably maintained at a pressure selected from thegroup consisting of: (i) <0.0001 mbar; (ii) 0.0001-0.001 mbar; (iii)0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar;(vii) 10-100 mbar; (viii) 100-1000 mbar; and (ix) >1000 mbar.

According to an embodiment analyte ions may be subjected to ElectronTransfer Dissociation (“ETD”) fragmentation in an Electron TransferDissociation fragmentation device. Analyte ions are preferably caused tointeract with ETD reagent ions within an ion guide or fragmentationdevice.

According to an embodiment in order to effect Electron TransferDissociation either: (a) analyte ions are fragmented or are induced todissociate and form product or fragment ions upon interacting withreagent ions; and/or (b) electrons are transferred from one or morereagent anions or negatively charged ions to one or more multiplycharged analyte cations or positively charged ions whereupon at leastsome of the multiply charged analyte cations or positively charged ionsare induced to dissociate and form product or fragment ions; and/or (c)analyte ions are fragmented or are induced to dissociate and formproduct or fragment ions upon interacting with neutral reagent gasmolecules or atoms or a non-ionic reagent gas; and/or (d) electrons aretransferred from one or more neutral, non-ionic or uncharged basic gasesor vapours to one or more multiply charged analyte cations or positivelycharged ions whereupon at least some of the multiply charged analytecations or positively charged ions are induced to dissociate and formproduct or fragment ions; and/or (e) electrons are transferred from oneor more neutral, non-ionic or uncharged superbase reagent gases orvapours to one or more multiply charged analyte cations or positivelycharged ions whereupon at least some of the multiply charge analytecations or positively charged ions are induced to dissociate and formproduct or fragment ions; and/or (f) electrons are transferred from oneor more neutral, non-ionic or uncharged alkali metal gases or vapours toone or more multiply charged analyte cations or positively charged ionswhereupon at least some of the multiply charged analyte cations orpositively charged ions are induced to dissociate and form product orfragment ions; and/or (g) electrons are transferred from one or moreneutral, non-ionic or uncharged gases, vapours or atoms to one or moremultiply charged analyte cations or positively charged ions whereupon atleast some of the multiply charged analyte cations or positively chargedions are induced to dissociate and form product or fragment ions,wherein the one or more neutral, non-ionic or uncharged gases, vapoursor atoms are selected from the group consisting of: (i) sodium vapour oratoms; (ii) lithium vapour or atoms; (iii) potassium vapour or atoms;(iv) rubidium vapour or atoms; (v) caesium vapour or atoms; (vi)francium vapour or atoms; (vii) C₆₀ vapour or atoms; and (viii)magnesium vapour or atoms.

The multiply charged analyte cations or positively charged ionspreferably comprise peptides, polypeptides, proteins or biomolecules.

According to an embodiment in order to effect Electron TransferDissociation: (a) the reagent anions or negatively charged ions arederived from a polyaromatic hydrocarbon or a substituted polyaromatichydrocarbon; and/or (b) the reagent anions or negatively charged ionsare derived from the group consisting of: (i) anthracene; (ii) 9,10diphenyl-anthracene; (iii) naphthalene; (iv) fluorine; (v) phenanthrene;(vi) pyrene; (vii) fluoranthene; (viii) chrysene; (ix) triphenylene; (x)perylene; (xi) acridine; (xii) 2,2′ dipyridyl; (xiii) 2,2′ biquinoline;(xiv) 9-anthracenecarbonitrile; (xv) dibenzothiophene; (xvi)1,10′-phenanthroline; (xvii) 9′ anthracenecarbonitrile; and (xviii)anthraquinone; and/or (c) the reagent ions or negatively charged ionscomprise azobenzene anions or azobenzene radical anions.

According to a particularly preferred embodiment the process of ElectronTransfer Dissociation fragmentation comprises interacting analyte ionswith reagent ions, wherein the reagent ions comprise dicyanobenzene,4-nitrotoluene or azulene reagent ions.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be described, byway of example only, and with reference to the accompanying drawings inwhich:

FIG. 1A shows a front view of a schematic of an ion mobility separator(IMS) according to a preferred embodiment of the present invention, FIG.1B shows a cross-sectional side view of a portion of the drift cell ofthe IMS device of FIG. 1A, and FIGS. 1C and 1D show different views ofthe embodiment of FIG. 1A;

FIG. 2 shows a schematic perspective view of an embodiment of the ionentry/exit device of the drift cell;

FIG. 3 shows a schematic of the electrical potentials that are appliedto the ion entry/exit device during a mode in which ions areinjected/loaded into the entry/exit device from outside of the driftcell;

FIG. 4 shows the electrical potentials that are applied to the ionentry/exit device during a mode in which ions are driven out of the ionentry/exit region and into the adjacent part of the drift cell;

FIG. 5A shows a schematic of a preferred embodiment of a spectrometercomprising the IMS device, and FIG. 5B shows a potential energy diagramof the DC potentials applied to the components of the spectrometer in amode in which ions are being accumulated in the ion entry/exit device ofthe drift cell;

FIGS. 6A and 6B show how the potentials applied to the spectrometer arealtered in preparation for moving ions from the ion entry/exit deviceinto the axially adjacent part of the IMS drift cell;

FIGS. 7A and 7B show the DC potentials applied to the spectrometer at astage when the ions are driven out of the ion entry/exit device into theadjacent part of the IMS drift cell; and

FIGS. 8A and 8B show the DC potentials applied to the spectrometer at astage when the ions are ejected from the drift cell at the ionentry/exit device.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

FIG. 1A shows a front view of a schematic of an ion mobility separator(IMS) according to a preferred embodiment of the present invention. TheIMS device 1 comprises a closed-loop drift cell 2 around which the ionsare guided in use. The drift cell 2 comprises a plurality of electrodesthat act to confine the ions to an axial path that extends around theclosed-loop drift cell 2. The drift cell 2 also comprises electrodesthat urge the ions along the axial length of the drift cell. The ionguide is filled with a background gas such that as the ions are urgedaround the drift cell 2 they collide with the gas molecules and separateaccording to their ion mobilities through the gas. The ions may be urgedaround the closed-loop drift cell 2 once or multiple times before beingextracted through an exit region 4. The ions may be urged around thedrift cell 2 by applying one or more electrical potential that travelsaxially along the drift cell 2, or less preferably by a static DCpotential gradient that is arranged axially along the drift cell 2.

FIG. 1B shows a cross-sectional side view of a portion of the drift cell2 of the IMS device of FIG. 1A. FIG. 1B shows an embodiment of anelectrode unit arrangement 5 that may be used to confine ions to theaxis of the ion guiding path in the drift cell 2. At a given point alongthe axial length of the ion guiding path, the path is preferably definedbetween two RF electrodes 6 that are spaced apart in a first directionand two DC electrodes 8 that are spaced in a second, preferablyorthogonal, direction. RF voltages are applied to the RF electrodes 6 soas to confine the ions between the RF electrodes 6, in the firstdirection. DC voltages are applied to the DC electrodes 8 so as toconfine the ions between the DC electrodes 8, in the second direction.The electrode unit 5 is repeated along the axial length of the driftcell 2 such that ions are confined in the drift cell 2 at all pointsaround the ion guide, except when ions are ejected from the ionentry/exit region 4, which will be described further below. Theelectrode units 5 are axially spaced along the ion guiding path and oneof more DC potential may be successively applied to successive electrodeunits 5 such that a travelling DC potential travels around the driftcell 2 and hence forces the ions around the drift cell. Alternatively,different DC potentials may be applied to successive electrode units 5around the ion guide such that a static DC gradient is applied along theaxis that forces the ions around the drift cell 2.

The upper and lower sides of the drift cell 2 may be formed from printedcircuit boards having the DC or RF electrodes 6,8 arranged thereon.Alternatively, or additionally, the radially inner and outer sides ofthe drift cell 2 may be formed from printed circuit boards having the RFor DC electrodes 6,8 arranged thereon.

FIG. 1C and FIG. 1D show an orthogonal view and a perspective view ofthe embodiment of FIG. 1A respectively. The drift cell 2 is arrangedinside a chamber 10 that is filled with drift gas. Ions are guided intoand out of the chamber 10 using RF ion guides 12,14. The RF ion guides12,14 are also coupled with the ion entry/exit region 4 of the driftcell 2 such that ions can be guided into the drift cell 2 and out of thedrift cell 2. In this embodiment, ions are guided into the chamber 10and into the entry/exit region 4 of the drift cell 2 by input ion guides12. If the ions are desired to be separated by their ion mobility thenthe ions are urged in an orthogonal direction to the ion entry directionand are urged around the oval or racetrack ion path of the drift cell 2.As the ions pass along the ion path they separate according to their ionmobility through the drift gas that is present in the chamber 10 andhence the drift cell 2. When ions are desired to be extracted from thedrift cell 2 they are ejected in a direction towards the exit RF ionguides 14. The ions are then guided out of the chamber 10 by the exition guides 14.

On the other hand, if ion mobility separation of the ions is notrequired then ion species can be caused to pass from the input ion guide12 to the output ion guide 14 directly through the entry/exit region 4of the drift cell 2 and without passing around the drift cell 2. Inother words, the drift cell 2 may be operated in a by-pass mode.

In a preferred mode of operation, it is possible to extract ions havinga desired range of ions mobilities from the drift cell 2. This isachieved by causing ions to traverse around the drift cell 2 so thatthey separate and then synchronising the activation of one or moreejection voltages at the ion entry/exit region 4 with the time at whichthe ions of interest are at the entry/exit region 4. The desired ionsare therefore ejected from the drift cell 2 and the other ion speciesremaining in the drift cell 2 can continue to pass through the driftcell 2 and separate according to ion mobility. Alternatively, theremaining ions may be discarded from the drift cell 2, for example, byremoval of the RF voltages from the electrodes 6 such that the ions areno longer confined within the drift cell 2.

The ejected ions having the desired ion mobilities can be immediatelytransported away from the drift cell 2 to a mass analyser or detector.Alternatively, such ions may be trapped in a storage region whilst thenext mobility cycle occurs in the drift cell 2 and until more ions ofthe same ion mobility range are ejected from the drift cell 2 into thestorage region. After sufficient mobility cycles have been performed toaccumulate the desired number of ions in the storage region, these ionsmay then be transported to an analyser for further analysis or to adetector. This method may be used to increase the ion signal of thedesired ions. Additionally, or alternatively, the desired ions that havebeen ejected from the drift cell 2 may be fragmented, activated ordissociated and then reintroduced back into the drift cell such that theion mobilities of the fragment, activated or product ions can beanalysed by the drift cell 2.

FIG. 2 shows a schematic perspective view of an embodiment of the ionentry/exit device 4 of the drift cell 2. The ion entry/exit device 4comprises two parallel, rectangular arrays of electrodes 20,22 that arespaced apart from each other. Each array of electrodes 20,22 comprises aplurality of electrodes arranged in rows and columns. Various electricalpotentials are applied to these electrodes so as to manipulate the ions,as will be described in more detail below. The device has four sidesthat extend between the four edges of the arrays 20,22. Two of theopposing sides are formed by end plates 24,26, wherein each end platehas an orifice 28,30 therein. One of the end plates 26 has an ioninjection orifice 30 for injecting ions into the device 4 from outsideof the drift cell 2. The opposing end plate 24 has an ion ejectionorifice 28 for ejecting ions out of the device 4 and the drift cell 2.The other two opposing sides are junctions with the drift electrodes 32of the main drift cell 2. One of the junctions, the entrance junction,allows ions to pass into the device 4 from within another part of thedrift cell 2. The other junction, the exit junction, allows ions to passout of the device 4 and into another part of the drift cell 2.

RF electrical potentials are applied to the electrodes in the arrays ofelectrodes 20,22 in order to confine ions in the direction between thearrays 20,22. The same phase RF potential is preferably applied to allof the electrodes in the same column of electrodes (a column extends inthe direction between the end plates 24,26 having orifices 28,30).Adjacent columns of electrodes are preferably maintained at different RFphases, preferably opposite RF phases. However, it is alternativelycontemplated that same phase RF potential may be applied to all of theelectrodes in the same row (a row extends in the direction parallel tothe apertured plates 24,26). Adjacent rows of electrodes are preferablymaintained at different RF phases, preferably opposite RF phases.

The ion entry/exit device 4 has plurality of modes of operation.According to a first mode of operation the device 4 is operated in amanner that injects or loads ions into the device 4 from outside of thedrift cell 2. The device 4 may also be operated in another mode thaturges ions out of the ion entry/exit device 4 into an adjacent part ofthe drift cell 2. The device 4 may also be operated in another modewhich ejects ions out of the device 4 to a region outside of the driftcell 2. These modes will now be described with reference to FIGS. 3 and4.

FIG. 3 shows a schematic of the electrical potentials that are appliedto the ion entry/exit device 4 and the adjacent parts of the drift cell2 on either side of the device 4 during a mode in which ions areinjected/loaded into the entry/exit device 4 from outside of the driftcell 2. The array of dark and light vertical bars 30 represent thepotentials applied to either or both of the electrode arrays 20,22 inthe ion entry/exit device 4. The colours of the vertical bars 30represent the RF phases applied to the electrodes in the arrays 20,22,e.g. light coloured vertical bars represent one RF phase and darkcoloured RF bars represent the opposite RF phase. The vertical heightsof the vertical bars 30 represent the magnitudes of the DC voltagesapplied to the electrodes in the array(s) 20,22. It can be seen thatrelatively high amplitude DC potentials are applied to all of theelectrodes in some of the rows of electrodes, and that relatively lowamplitude DC potentials are applied to all of the electrodes in theadjacent rows of electrodes. During the mode in which ions areinjected/loaded into the device 4, the DC potentials applied to theelectrodes in the arrays 20,22 are varied with time such that the highDC voltages are successively applied to successive rows of electrodes ina direction from the ion injection orifice 30 towards the ion ejectionorifice 28, and such that DC potential barriers travel in the directionfrom the ion injection orifice 30 towards the ion ejection orifice 28.Simultaneously, the low DC voltages are successively applied tosuccessive rows of electrodes in a direction from the ion injectionorifice 30 towards the ion ejection orifice 28. This causes ions to beforced into the ion entry/exit device 4 by the high amplitude DCvoltages, wherein the ions travel in the regions of low DC voltages. Theend plate having the exit orifice 28 may be maintained at a DC or RFpotential such that ions are prevented from exiting the ion entry/exitdevice 4 during loading/injection of ions. Alternatively, oradditionally, the amplitude of the high DC potentials may decrease asthey travel in the direction towards the exit orifice 28. Alternatively,or additionally, a row of electrodes proximal to the exit orifice 28 maybe maintained at high DC potentials so that the ions cannot be forcedpast this row and out of the ion entry/exit device 4 during loading.

The horizontally elongated bars 32 in FIG. 3 represent the potentials ofelectrodes in regions of the drift cell 2 that are adjacent to the ionentry/exit device 4. The colours of these horizontal bars represent theRF phases applied to the electrodes, e.g. light-coloured bars representone RF phase and dark-coloured bars represent the opposite RF phase. Thevertical heights at which the horizontally elongated bars 32 are locatedrepresent the magnitudes of the DC voltages applied to the electrodes.As can be seen, most of the horizontally elongated bars 32 are at arelatively low DC potential, but some of these bars are at a higher DCpotential. These higher DC potentials are successively applied tosuccessive electrodes along the axial length of the drift cell 2 so thata DC potential barrier travels along the axial length of the drift cell2 and drives ions around the drift cell 2, which will be described inmore detail in relation to FIG. 4.

Referring again to FIG. 3, the vertical heights at which the uppersurfaces of the horizontally elongated bars 32 are located represent themagnitudes of the DC voltages applied to the electrodes. It can be seenthat the magnitude of the low DC potentials applied to the electrodearrays 20,22 during ion loading/injection is smaller than the DCpotentials at which the axially adjacent regions of the drift cell 2 ismaintained. As such, the ions are prevented from passing from the ionentry/exit region 4 into the adjacent regions of the drift cell 2 duringthe ion loading/injection mode.

Once the ions have been loaded/injected into the ion entry/exit device4, all of the electrodes in the array 20,22 may be maintained at therelatively low DC potential, i.e. there is no longer a need to driveions in the direction between the end plates 24,26 having the orifices28,30 and so the high DC potentials may be replaced by low DCpotentials. The two end plates 24,26 may be maintained at DC or RFpotentials that prevent ions from exiting through the end plates 24,26.The DC potentials applied to the electrodes in the arrays 20,22 may thenbe increased to the same value as the low DC potentials of the axiallyadjacent regions of the drift cell 2. There is then no DC barrierbetween the ion entry/exit region 4 and the axially adjacent portions ofthe drift cell 2. As such, ions may then pass easily from the ionentry/exit device 4 into the adjacent portion of the drift cell 2 so asto be separated according to their ion mobilities, as will be describedwith reference to FIG. 4.

FIG. 4 shows the electrical potentials that are applied to the ionentry/exit device 4 and the axially adjacent parts of the drift cell 2during a mode in which ions are driven out of the ion entry/exit region4 and into the adjacent part of the drift cell 2. As described above,after ions have been loaded/injected into the ion entry/exit device 4the DC potentials applied to the arrays of electrodes 20,22 are raisedto correspond to the DC potentials of the adjacent parts of the driftcell 2. As such, there is no longer a DC barrier between the ionentry/exit device 4 and the adjacent parts of the drift cell. As shownin FIG. 4, the DC potentials applied to two columns of electrodes in theelectrode arrays 20,22 are then increased to high DC voltages relativeto the other electrodes in the arrays 20,22. These high DC voltages aresuccessively applied to successive columns in the arrays 20,22 such thatthe high DC voltages move along the arrays in the axial direction of thedrift cell 2, as indicated by the arrow in FIG. 4. This causes the ionsto be driven out of the ion entry/exit device 4 and through the exitjunction. The ions then pass into the axially adjacent portion of thedrift region 2. The high DC voltages that drove the ions out of the ionentry/exit device 4 may then be successively applied to successiveelectrodes along the axial length of the remainder of the drift region 2so as to continuously drive the ions around the entire drift region 2.Examples of such voltages are shown by the relatively high horizontallyelongated bars in FIG. 4.

The ions are driven around the closed-loop drift cell 2 by thetravelling DC voltages and back into the ion entry/exit device 4 throughthe entrance junction. The ions may be ejected from the drift cell 2 atthis point, as will be described in more detail below. Alternatively,the ions may again be driven through the ion entry/exit device 4 byapplying the travelling DC potentials to the columns of electrodes inthe electrode arrays 20,22 and then driven around the drift cell 2 bythe travelling DC potentials applied to the remainder of the drift cellelectrodes. The ions may be driven around the drift cell 4 by thisprocess as many times as is desired, until the ions have separatedaccording to their ion mobility as desired. In this mode, thetranslation of the high DC potentials that drive ions through the ionentry/exit device 4 and into the axially adjacent part of the driftregion 2 is preferably synchronised with the translation of the high DCpotentials around the rest of the drift region. As such, the ionentry/exit region 4 is substantially ion-optically identical to theremainder of the drift region 2 during the mode of operation in whichthe ions are translated around the closed-loop drift cell a plurality oftimes.

When it is desired to eject ions from the drift cell, the DC potentialsapplied to the arrays of electrodes 20,22 in the ion entry/exit region 4may be lowered again relative to the adjacent parts of the drift cell 2as shown in FIG. 3. DC potentials may then be applied to the arrays ofelectrodes 20,22 so as to drive ions in the direction from the injectionorifice 30 of the injection end plate 26 to the ejection orifice 28 ofthe ejection end plate 24. This is performed in the same manner as theion loading/ejection mode of FIG. 3, except that in the ejection modethere is no potential barrier preventing the ions exiting the ionentry/exit device through the ejection orifice 30 of the ejection endplate 26. It will be appreciated that alternatively the ions could beejected from the ion entry/exit device 4 through the same orifice 30that they were loaded/injected by translating the high DC potentials inthe opposite direction to the loading/injection direction.

The ion entry/exit region 4 may operate in a bypass mode in which ionsare not desired to be driven around the closed-loop drift cell 2, and inwhich the ions are not caused to separate. This mode is the same as thatdescribed in relation to FIG. 3, except that the ions simply passdirectly from the entrance orifice 30 and out of the exit orifice 28without being transmitted orthogonally into the axially adjacent portionof the drift cell 2. The ions may be prevented from passing into theaxially adjacent portion of the closed-loop drift cell 2 by the DCpotentials on the electrodes arrays 20,22 being lower than those of theadjacent parts of the drift cell 2. The ions may or may not be driventhrough the ion entry/exit region 4 by the high DC potentials describedin relation to FIG. 3.

FIG. 5A shows a schematic side view of a preferred embodiment of aspectrometer comprising the IMS device. The spectrometer comprises adrift gas chamber 10, an ion trap 40, a helium cell 42, an ionaccumulation cell 44, the IMS device 2, an exit cell 46 and an iontransfer cell 48. Electrode gates 50-58 are arranged between the abovedescribed successive components. In particular, an entrance gate 54 isarranged upstream of the ion entry/exit device 4 and an exit gate 56 isarranged downstream of the ion entry/exit device 4. The IMS device 2corresponds to that shown in FIG. 1C.

FIG. 5B shows a potential energy diagram of the DC potentials applied tothe components of the spectrometer in a mode in which ions are beingaccumulated in the ion entry/exit device 4 of the drift cell 2. Ions arereleased from the ion trap 40 and are then driven through the heliumcell 42 by an axial electric field. The ions then pass through the ionaccumulation cell 44 and into the ion entry/exit device 4 through theion entrance orifice 30 in the entrance end plate 26 described above inrelation to FIG. 2. The DC potentials of the electrodes in the electrodearrays 20,22 of the ion entry/exit device 4 are maintained lower thanthe DC potentials applied to the accumulation cell 44, the entrance gate54 and the exit gate 56. As such, ions are axially, trapped andaccumulate in the ion entry/exit device 4. The ions enter the ionentry/exit device 4 through the entrance orifice 30 of the entrance endplate 26 described above in relation to FIG. 2. A travelling DC wave maybe applied to the rows of electrodes in the electrode arrays 20,22 inorder to urge ions into the ion entry/exit device 4, as described withreference to FIG. 3. The DC potential of the IMS drift cell 2 (excludingthe ion entry/exit device 4) is represented by the horizontal line thatis parallel and vertically above the line representing the DC voltageapplied to the arrays 20,22 of the ion entry/exit device 4. Thepotential difference represented by the gap between these two linesprevents ions from passing out of the ion entry/exit device 4 and intothe axially adjacent parts of the IMS drift cell 2.

FIGS. 6A and 6B correspond to FIGS. 5A and 5B, except that they show howthe potentials applied to the spectrometer are altered in preparationfor moving ions from the ion entry/exit device 4 into the axiallyadjacent part of the IMS drift cell 2. As shown by the arrows in FIG.6B, the DC potentials of the entrance gate 54, array electrodes 20,22and exit gate 56 are raised to the DC potentials illustrated by thehorizontal dashed lines. The DC potentials applied to the arrays ofelectrodes 20,22 are then equivalent to the DC potentials applied to theadjacent parts of the IMS drift cell 2, and hence there is no DC barrierpreventing ions from passing from the ion entry/exit device 4 into theadjacent part of the IMS drift cell 2.

FIGS. 7A and 7B correspond to FIGS. 6A and 6B, except that they show thepotentials at a stage when the ions are driven out of the ion entry/exitdevice 4 into the adjacent part of the IMS drift cell 2. As describedabove with reference to FIG. 4, the ions are driven out of the exitaperture 28 in the apertured exit plate 24 by applying DC travellingpotentials to the columns of electrodes in the arrays of electrodes20,22. These travelling potentials are illustrated by the series ofparallel horizontal lines 60 in FIG. 7B. The ions are then driven aroundthe drift cell 2 by travelling DC potentials such that the ions separateaccording to their ion mobilities, as has been described above. When theions have passed around the drift cell 2 the desired number of times,the ions may be ejected at the ion entry/exit device 4. The length oftime the potentials of the electrode arrays 20,22 are in the mode shownin FIG. 7B dictates how many passes the ions of given ion mobility makearound drift cell 2.

FIGS. 8A and 8B correspond to FIGS. 7A and 7B, except that they show theDC potentials applied to the spectrometer at a stage when the ions areejected from the drift cell 2 at the ion entry/exit device 4. As shownby the arrows in FIG. 8B, the DC potentials of the entrance gate 54,array electrodes 20,22 and exit gate 56 are lowered to the DC potentialsillustrated by the horizontal dashed lines. The DC potentials of theentrance gate 54, array electrodes 20,22, exit gate 56, exit cell 45 andion transfer cell 48 progressively decrease such that the ions are urgedout of the ion entry/exit device 4 and along the spectrometer towardsthe ion transfer cell 48. The ions leave the ion entry/exit device 4through the exit orifice 28 of the exit end plate 24 described above inrelation to FIG. 2. A travelling DC wave is applied to the rows ofelectrodes in the electrode arrays 20,22 in order to urge ions out ofthe exit orifice 28. This is represented by the series of vertical lines62 in the electrode array region of FIG. 8B.

Varying the potentials applied to the ion entry/exit device 4 relativeto the remainder of the drift cell 2 during loading or ejection of ionsat the ion entry/exit device 4 facilitates ion entry and exit from thedrift cell 2 without having to alter the potentials of the othercomponents of the spectrometer that are upstream or downstream. Thisalso enables a bypass mode in which ions are not separated in the driftcell 2. For example, the DC potentials of the entrance gate 54,electrode arrays 20,22 and exit gate 56 may be made equivalent to the DCpotentials of the accumulation cell 44 and exit cell 46 such that ionspass continuously from the accumulation cell 44, through the ionentry/exit device 4 and into the exit cell 46 without being separated inthe drift cell 2.

The travelling DC waves applied to the drift cell 2 outside of the ionentry/exit device 4 may be operated continually during the above modes.

Although the present invention has been described with reference topreferred embodiments, it will be understood by those skilled in the artthat various changes in form and detail may be made without departingfrom the scope of the invention as set forth in the accompanying claims.

For example, although travelling DC potentials have been described asbeing used for driving ions around the region of the drift cell 2outside of the ion entry/exit device 4, static DC gradients may be usedinstead for this purpose.

It will be appreciated that drift cells 2 having continuous ion guidingpaths of shapes other than circular or oval paths are also contemplatedas being within the scope of the present invention.

The ion entry/exit device 4 may be used for manipulating ions in systemsother than ion mobility drift cells 2. For example, the ion entry/exitdevice 4 may be used to inject ion into or eject ions from another typeof device.

The drift cell 2 (or other type of device) need not be a closed-loopdevice around which ions are guided. For example, the ion entry/exitdevice 4 could be used in a linear device. The ions may pass along sucha non-closed loop device once, or may be reflected along the devicemultiple times.

The geometry of the electrode arrays 20,22 may be varied and need not bearrays having columns and rows of electrodes.

The direction of the travelling DC potentials in the electrode arraysmay be changed or may provide multiple directional travel options.

1. A method of introducing and ejecting ions from an ion mobilityseparation device, said method comprising: providing an ion entry/exitregion having at least two arrays of electrodes; and operating the ionentry/exit region in a first mode, wherein DC potentials aresuccessively applied to successive electrodes of at least one of theelectrode arrays in a first direction such that a potential barriermoves along the at least one array in the first direction and drivesions into and/or out of the region in the first direction.
 2. The methodof claim 1, wherein said at least two arrays of electrodes are arrangedparallel to each other.
 3. The method of claim 1, wherein each array ofelectrodes comprises a plurality of electrodes arranged in rows andcolumns; and wherein in said first mode said DC potentials are appliedto the electrodes in a first row and are then successively applied todifferent rows of electrodes such that said potential barrier movesalong the array in the first direction; and/or wherein in a second modeDC potentials are applied to the electrodes in a first column and arethen successively applied to different columns of electrodes such that apotential barrier moves along the array in a second, differentdirection.
 4. The method of claim 1, further comprising supplying RFvoltages to said arrays of electrodes so as to confine ions in thedirection between the arrays.
 5. The method of claim 1, wherein themethod is operated in the first mode and ions are loaded into the regionin the first direction, and the method is then operated in a second modeand these ions are ejected from the device in a second, differentdirection.
 6. The method of claim 1, comprising: temporally separatingions according to a physicochemical property prior to their entry intothe ion entry/exit region; then receiving the ions in the ion entry/exitregion; operating the ion entry/exit region in the first mode so thatthe temporally separated ions are ejected from the region in the firstdirection; and temporarily operating the ion entry/exit region in asecond mode so as to selectively eject ions having a selected value, orrange of values, of said physicochemical property from the region. 7.(canceled)
 8. The method of claim 1, further comprising ejecting saidions from the ion entry/exit region into an ion guide; wherein the ionguide comprises electrodes and the method comprises applying DC voltagesto the electrodes of the ion guide so as to drive ions along thelongitudinal axis of the ion guide; and wherein either a static DCpotential gradient is applied along the axial length of the ion guide soas to drive ions along said longitudinal axis or wherein one or more DCpotentials is applied to successive electrodes along the axial length ofthe ion guide such that a DC potential barrier travels along the lengthof the ion guide and drives ions along the ion guide.
 9. (canceled) 10.The method of claim 8, wherein ions are driven out of the ion entry/exitregion, into the ion guide and are then reintroduced back into the ionentry/exit region.
 11. The method of claim 10, wherein the potentialbarrier in the ion entry/exit region urges the reintroduced ions out ofthe ion entry/exit region again so that the ions and pass through theion guide again.
 12. (canceled)
 13. The method of claim 10, wherein theions pass through the ion guide ≥x times, wherein x is 2, 3, 4, 5, 6, 7,8, 9, 10, 15 or
 20. 14. The method of claim 8, wherein the ionentry/exit region and/or ion guide forms an ion mobility separator inwhich the ions separate along the longitudinal axis according to theirion mobilities.
 15. The method of claim 14, wherein the ions separateaccording to their ion mobilities as they pass along the ion guide, andwherein the ion entry/exit region is then switched so as to eject atleast some of the separated ions out of the device into a further ionguide, ion trap, or ion processing device.
 16. The method of claim 15,wherein the ion entry/exit region is temporarily switched such that onlyions of a first ion mobility, or first range of ion mobilities, thathave passed along the ion guide are ejected out of the ion entry/exitregion, whilst other ions having a second ion mobility, or second rangeof ion mobilities, continue on to pass through the ion guide again. 17.The method of claim 15, wherein the selectively ejected ions are stored,mass analysed, fragmented to form fragment ions, or reacted with ions ormolecules to form product ions within said further ion guide, ion trap,or ion processing device.
 18. The method of claim 15, comprisingreintroducing the selectively ejected ions, fragment ions or productions into the ion entry/exit region such that the reintroduced ions passinto the ion guide again.
 19. (canceled)
 20. (canceled)
 21. A method ofintroducing and ejecting ions from an ion entry/exit region, said methodcomprising: providing an ion entry/exit region having at least one arrayof electrodes; operating the device in a first mode, wherein DCpotentials are successively applied to successive electrodes of theelectrode array in a first direction such that a potential barrier movesalong the array in the first direction and drives ions into and/or outof the region in the first direction.
 22. (canceled)
 23. (canceled) 24.(canceled)
 25. An ion entry/exit device for a mass spectrometer and/orion mobility spectrometer, said device comprising: at least one array ofelectrodes; at least one DC voltage supply; and control means forvarying the electrical potentials applied to the electrodes of said atleast one array with time; wherein in a first mode of operation saidcontrol means successively applies DC potentials to successiveelectrodes of the at least one array in a first direction such that apotential barrier moves along the at least one array in the firstdirection for driving ions into and/or out of the device in the firstdirection.
 26. (canceled)
 27. A mass spectrometer and/or ion mobilityspectrometer comprising an ion entry/exit device as claimed in claim 25.28. The ion entry/exit device of claim 25, wherein said at least onearray of electrodes is at least two of said arrays of electrodes. 29.The method of claim 1, wherein said at least two arrays of electrodesare formed from printed circuit boards.